Megalin genetic polymorphisms and individual sensitivity to the ototoxic effect of cisplatin
| Autor: | A G am Zehnhoff-Dinnesen, Heribert Jürgens, C Lanvers, Joachim Boos, D. Deuster, Ulrike Peters, L Riedemann |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Genotype Hearing loss Antineoplastic Agents Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Nephrotoxicity Ototoxicity Neoplasms Internal medicine Genetics medicine Humans Inner ear Allele Child Hearing Disorders Pharmacology Cisplatin Polymorphism Genetic Reverse Transcriptase Polymerase Chain Reaction Odds ratio Anatomy medicine.disease Low Density Lipoprotein Receptor-Related Protein-2 Endocrinology medicine.anatomical_structure Child Preschool Audiometry Pure-Tone Molecular Medicine Female medicine.symptom medicine.drug |
| Zdroj: | The Pharmacogenomics Journal. 8:23-28 |
| ISSN: | 1473-1150 1470-269X |
| DOI: | 10.1038/sj.tpj.6500455 |
| Popis: | Ototoxicity and nephrotoxicity are dose-limiting side effects of cisplatin. Megalin, a member of the low-density lipoprotein receptor family, is highly expressed in renal proximal tubular cells and marginal cells of the stria vascularis of the inner ear - tissues, which accumulate high levels of platinum-DNA adducts. On the assumption that the mechanisms of cisplatin-induced nephro- and ototoxicity involve megalin we analyzed the incidence of the non-synonymous single nucleotide polymorphisms (SNP) rs2075252 and rs4668123 in 25 patients who developed a distinct hearing loss during cisplatin therapy and in 25 patients without hearing impairment after cisplatin therapy. We found no association between cisplatin-induced ototoxicity and any allele of rs4668123 but observed a higher frequency of the A-allele of rs2075252 in the group with hearing impairment than in the group with normal hearing after cisplatin therapy (0.32 versus 0.14) (chi(2)=5.83, P0.02; odds ratio: 3.45; 95% confidence interval: 1.11-11.2) indicating that SNPs at the megalin gene might impact the individual susceptibility against cisplatin-induced ototoxicity. |
| Databáze: | OpenAIRE |
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